Low incidence of UPD in spontaneous abortions beyond the 5th gestational week

Abstract

Approximately 15 ± 20% of all clinically recognised pregnancies abort, most commonly between 8 ± 12 gestational weeks. While the majority of early pregnancy losses is attributed to cytogenetic abnormalities, the aetiology of approximately 40% of early abortions remains unclear. To determine additional factors causing spontaneous abortions we retrospectively searched for uniparental disomies (UPD) in 77 cytogenetically normal diploid spontaneous abortions. In all cases an unbalanced chromosome anomaly was ruled out by cytogenetic investigation of chorionic/amniotic membranes and/or chorionic villi. For UPD screening microsatellite analyses were performed on DNA of abortion specimens and parental blood using highly polymorphic markers showing UPD in two cases. The distribution of markers analysed indicated maternal heterodisomy for chromosome 9 (UPhD(9)mat) in case 1 and paternal isodisomy for chromosome 21 (UPiD(21)pat) in case 2. The originating mechanism suggested was monosomy complementation in UPiD(21)pat and trisomy rescue in UPhD(9)mat. In the case of UPhD(9)mat purulent chorioamnionitis was noted and a distinctly growth retarded embryo of 3 cm crown-rump length showing no gross external malformations. Histological analysis in the case of UPiD(21)pat suggested a primary anlage defect. Our results indicate that less than 3% of genetically unexplained pregnancy wastage is associated with total chromosome UPD. UPD may contribute to anlage defects of human conception. Chromosome aneuploidy correction can occur in very early cleavage stages. More research, however, ought to be performed into placental mosaicism to further clarify timing and mechanisms involved in foetal UPD. European Journal of Human Genetics (2001) 9, 910 ± 916.

Improved assay performance of single nucleotide polymorphism array over conventional karyotyping in analyzing products of conception

“…However, UPD also causes abnormal embryonic/fetal development or even miscarriage, although the frequency of UPD-associated miscarriage may be low, which was estimated to occur in < 3% of miscarriage cases. 21,22 Several studies found that UPDs, for example, with maternal uniparentalheterodisomy of chromosome 9, 21 paternal UPD of chromosome 14, 22 maternal uniparentalisodisomy and uniparentalheterodisomy of chromosome 16, 23 and paternal uniparentalisodisomy of chromosome 21, 21 could cause miscarriage. Moreover, it was well known that wholegenome UPD was not compatible with life, and paternal origin would lead to complete hydatidiform mole, resulting in embryonic death.…”

Paternal uniparental disomy of chromosome 14 and unique exchange of chromosome 7 in cases of spontaneous abortion

“…In the literature to date, only three cases of UPDs 9, 16, and 21 have been found among spontaneous abortions (Fritz et al 2001;Kondo et al 2004), and the present case is the first report of UPD 14 in a spontaneous abortion. In other reports, the association of UPDs with spontaneous abortions has not been found (Shaffer et al 1998;Smith et al 1998).…”

“…To date, few UPD cases have been found among spontaneous abortions (Fritz et al 2001;Kondo et al 2004). To investigate the involvement of UPDs, we analyzed the chromosomal origin of spontaneous abortions in detail using microsatellite polymorphic markers and found UPD of chromosome 14 and a unique exchange of chromosome 7 in cases of spontaneous abortion.…”

Reply: Questions about the accuracy of polar body analysis for preimplantation genetic screening

“…Furthermore, our study was underpowered to estimate the actual incidence of correction events in the clinical PGS population. However, our data are well matched with a retrospective search for UPD in 77 cytogenetically normal diploid spontaneous abortions, indicating that 2.5% of genetically unexplained miscarriages were associated with whole chromosome UPD (Fritz et al, 2001). We thus look forward to see additional data from blastocyst stage PGS cycles using higher resolution chromosomal screening tests.…”